Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IGlarLixi (REMIT-iGL)

The purpose of the study is to determine whether in patients with early type 2 diabetes, a short-term intensive metabolic intervention comprising iGlarLixi, metformin, and lifestyle approaches will be superior to standard diabetes therapy in achieving sustained diabetes remission.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: iGlarLixi; Drug: Insulin Glargine; Drug: Metformin; Behavioral: Lifestyle therapy

Detailed Description

This is a multicentre, open-label, randomized controlled trial in 160 patients with recently-diagnosed T2DM. Participants will be randomized to 2 treatment groups: (a) a 12-week course of treatment with iGlarLixi, metformin and lifestyle therapy, and (b) standard diabetes therapy, and followed for a total of 64 weeks (1 year and 3 months). In all participants with HbA1C<7.3% at the 12 week visit, glucose-lowering medications will be discontinued and participants will be encouraged to continue with lifestyle modifications and regular glucose monitoring. Participants with HbA1C ≥ 7.3% at this visit or who experience hyperglycemia relapse after stopping drugs will receive standard glycemic management as informed by the current Canadian Diabetes Association clinical practice guidelines.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • University of Calgary
  • Ontario
    • Burlington, Ontario, Canada, M4G 3E8
      • LMC
    • Cambridge, Ontario, Canada, N1R 7L6
      • Joanne Liutkus
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University
    • London, Ontario, Canada, N6A 4V2
      • St. Joseph's Hospital
    • London, Ontario, Canada, N6G 2M1
      • Western University
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. men and women aged 30-80 years;
2. type 2 diabetes mellitus within 5 years of diagnosis;
3. stable diabetes drug regimen in the 10 weeks before randomization;
4. HbA1c 6.5-9.5% on no glucose lowering drugs, or </= 8.5% on 1 glucose-lowering drug, or </= 8.0% on 2 glucose lowering drugs;
5. body mass index >/= 23 kg/m2;
6. ability and willingness to perform self-monitoring of capillary blood glucose (SMBG);
7. ability and willingness to self-inject iglarlixi; and
8. provision of informed consent.

Exclusion Criteria:

1. current use of insulin therapy;
2. history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance;
3. history of end-stage renal disease or renal dysfunction as evidenced by eGFR<45 mL/min/1.73 m2 by MDRD formula;
4. history of lactic acidosis or diabetic ketoacidosis;
5. active liver disease or elevated alanine transferase (ALT) levels >\= 2.5 times upper limit of normal at the time of enrolment;
6. history or clinical suspicion of pancreatitis or medullary thyroid cancer, or a calcitonin level >/= 20 pg/ml;
7. cardiovascular disease (unless cleared for a moderate intensity exercise program by a specialist) including: i. acute coronary syndrome, hospitalization for unstable angina, myocardial infarction, or revascularization with coronary artery bypass grafting or percutaneous coronary intervention; ii. peripheral vascular disease, valvular heart disease, cardiomyopathy, aortic dissection, tachyarrhythmias, bradyarrhythmias, prior stroke or TIA; iii. prior hospitalization for heart failure; or iv. ECG findings concerning for ischemic heart disease (i.e. pathological Q-waves, ST-segment-T-wave abnormalities in contiguous leads, left anterior hemiblock, left bundle branch block, second or third degree atrioventricular block).
8. history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;
9. history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;
10. history of any major illness with a life expectancy of < 3 years;
11. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
12. excessive alcohol intake, acute or chronic;
13. currently pregnant, or breastfeeding, or not using a reliable method of birth control for the duration of the trial in all females with childbearing potential;
14. inability to take glargine, lixisenatide or metformin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Drug: iGlarLixi - sc injection; Drug: metformin - oral administration; Drug: insulin glargine - sc injection; Behavioral: lifestyle therapy, diet and exercise	Drug: iGlarLixi; Dose is titrated to achieve fasting normoglycemia; Other Names: glargine insulin / lixisenatide; Drug: Insulin Glargine; In those who need additional insulin or who cannot tolerate iGlarLixi, insulin glargine will be used. Dose is titrated to achieve fasting normoglycemia.; Other Names: Lantus; Drug: Metformin; Dose is titrated to 2000 mg daily or maximal tolerated dose; Behavioral: Lifestyle therapy; Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving; Other Names: diet and exercise
No Intervention: Standard Care; Standard glycemic care as informed by the current clinical practice guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The first occurrence of diabetes relapse	64 weeks of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants achieving drug-free diabetes remission	Diabetes remission is defined as HbA1C < 6.5% off diabetes drugs for at least 12 weeks	24 weeks after randomization
Number of participants achieving drug-free normoglycemia defined as HbA1C < 6.0% off diabetes drugs for at least 12 weeks		24 weeks after randomization
Percentage of weight loss from baseline	(Weight at randomization - weight at 12 weeks)/(weight at randomization)	12 weeks
Change in waist circumference from baseline	(Waist circumference at 12 weeks - weight circumference at randomization)	12 weeks
Glycated hemoglobin (HbA1C)	Expressed in Diabetes Control and Complications Trial (DCCT) units	12 weeks

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Sanofi
• Investigators: Principal Investigator: Natalia McInnes, MD, McMaster University; Principal Investigator: Hertzel Gerstein, MD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2017
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: April 23, 2017
• First Submitted That Met QC Criteria: April 23, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Exercise; Metformin; Diet; Lifestyle; iGlarLixi
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Lixisenatide
• Other Study ID Numbers: REMIT-iGlarLixi

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No